Gounder, M. M., Mahoney, M. R., Van Tine, B. A., Ravi, V., Attia, S., Deshpande, H. A., Gupta, A. A., Milhem, M. M., Conry, R. M., Movva, S., Pishvaian, M. J., Riedel, R. F., Sabagh, T., Tap, W. D., Horvat, N., Basch, E., Schwartz, L. H., Maki, R. G., Agaram, N. P., Lefkowitz, R. A., Mazaheri, Y., Yamashita, R., Wright, J. J., Dueck, A. C., Schwartz, G. K. (December 2018) Sorafenib for Advanced and Refractory Desmoid Tumors. N Engl J Med, 379 (25). pp. 2417-2428. ISSN 0028-4793
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Abstract
BACKGROUND: Desmoid tumors (also referred to as aggressive fibromatosis) are connective tissue neoplasms that can arise in any anatomical location and infiltrate the mesentery, neurovascular structures, and visceral organs. There is no standard of care. METHODS: In this double-blind, phase 3 trial, we randomly assigned 87 patients with progressive, symptomatic, or recurrent desmoid tumors to receive either sorafenib (400-mg tablet once daily) or matching placebo. Crossover to the sorafenib group was permitted for patients in the placebo group who had disease progression. The primary end point was investigator-assessed progression-free survival; rates of objective response and adverse events were also evaluated. RESULTS: With a median follow-up of 27.2 months, the 2-year progression-free survival rate was 81% (95% confidence interval [CI], 69 to 96) in the sorafenib group and 36% (95% CI, 22 to 57) in the placebo group (hazard ratio for progression or death, 0.13; 95% CI, 0.05 to 0.31; P<0.001). Before crossover, the objective response rate was 33% (95% CI, 20 to 48) in the sorafenib group and 20% (95% CI, 8 to 38) in the placebo group. The median time to an objective response among patients who had a response was 9.6 months (interquartile range, 6.6 to 16.7) in the sorafenib group and 13.3 months (interquartile range, 11.2 to 31.1) in the placebo group. The objective responses are ongoing. Among patients who received sorafenib, the most frequently reported adverse events were grade 1 or 2 events of rash (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). CONCLUSIONS: Among patients with progressive, refractory, or symptomatic desmoid tumors, sorafenib significantly prolonged progression-free survival and induced durable responses. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT02066181 .).
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > neoplasms diseases & disorders > cancer > drugs and therapies > chemotherapy bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL labs > Maki lab |
| Depositing User: | Matthew Dunn |
| Date: | 20 December 2018 |
| Date Deposited: | 26 Dec 2018 22:15 |
| Last Modified: | 20 Feb 2024 20:01 |
| PMCID: | PMC6447029 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/37523 |
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